Antibody therapeutics that bind OprF
Abstract
There is disclosed compositions and methods relating to or derived from anti-OprF and anti-OprI antibodies. More specifically, there is disclosed fully human antibodies that bind OprF and OprI, OprF and OprI-antibody binding fragments and derivatives of such antibodies, and OprF and OprI-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having Pseudomonas aeruginosa infections. There is disclosed a method for treating or preventing Pseudomonas aeruginosa infections, wherein the disease is selected from the group consisting of burns, surgical site infections, diabetic foot ulcers, infected wounds, and cystic fibrosis.
Claims
exact text as granted — not AI-modifiedWe claim:
1. A recombinant fully human anti-OprF antibody that binds to OprF, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain selected from the group consisting of
a) a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 3, and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 4,
b) a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 5, and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 6, and
c) a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 7, and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 8.
2. The recombinant fully human anti-OprF antibody of claim 1 , wherein the antibody has heavy chain/light chain variable domain sequences selected from the group consisting of SEQ ID NO. 3/SEQ ID NO. 4, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.
3. The recombinant fully human anti-OprF antibody of claim 1 , wherein the antibody is classified as an isotype selected from the group consisting of: IgG, IgM, IgD, IgA, and IgE.
4. A recombinant fully human anti-OprF antibody, or an antigen-binding fragment thereof, that binds to OprF, wherein the antibody, or antigen binding fragment, comprises a heavy chain variable domain and a light chain variable domain selected from the group consisting of
a) a heavy chain variable domain comprising complementarity determining regions (CDRs) as set forth in SEQ ID NO. 3, and a light chain variable domain comprising CDRs as set forth in SEQ ID NO. 4;
b) a heavy chain variable domain comprising CDRs as set forth in SEQ ID NO. 5, and a light chain variable domain comprising CDRs as set forth in SEQ ID NO. 6; and
c) a heavy chain variable domain comprising CDRs as set forth in SEQ ID NO. 7, and a light chain variable domain comprising CDRs as set forth in SEQ ID NO. 8.
5. The recombinant fully human anti-OprF antibody of claim 4 , which is a Fab fragment.
6. The fully human anti-OprF antibody Fab fragment of claim 5 , wherein the Fab fragment has a heavy chain/light chain variable domain sequences selected from the group consisting of SEQ ID NO. 3/SEQ ID NO. 4, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.
7. A single chain human anti-OprF antigen-binding fragment that binds to OprF, comprising a heavy chain variable domain and a light chain variable domain selected from the group consisting of
a) a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 3 and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 4;
b) a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 5 and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 6; and
c) a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 7, and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 8,
wherein a peptide linker connects the heavy chain variable domain and the light chain variable domain.
8. The single chain human anti-OprF antigen-binding fragment of claim 7 , comprising heavy chain/light chain variable domain sequences selected from the group consisting of SEQ ID NO. 3/SEQ ID NO. 4, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.
9. The recombinant fully human anti-OprF antigen-binding fragment of claim 4 , which is a single chain antibody.
10. The recombinant fully human antibody, or antigen-binding fragment thereof, of claim 4 , comprising heavy chain/light chain variable domain sequences as set forth in SEQ ID NO. 3/SEQ ID NO. 4, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.
11. A pharmaceutical composition comprising the recombinant fully human anti-OprF antibody, or antigen binding fragment thereof, of claim 4 , and a pharmaceutically acceptable excipient.
12. A method for treating a Pseudomonas aeruginosa infection in a subject, comprising administering an effective amount of an anti-OprF polypeptide to a subject in need thereof, wherein the anti-OprF polypeptide is selected from the group consisting of a recombinant fully human antibody, a fully human antibody Fab fragment, and a fully human single chain antibody, and wherein the polypeptide comprises a heavy chain variable domain and a light chain variable domain selected from the group consisting of:
a) a heavy chain variable domain comprising CDRs as set forth in SEQ ID NO. 3 and a light chain variable domain comprising CDRs as set forth in SEQ ID NO. 4;
b) a heavy chain variable domain comprising CDRs as set forth in SEQ ID NO. 5 and a light chain variable domain comprising CDRs as set forth in SEQ ID NO. 6; and
c) a heavy chain variable domain comprising CDRs as set forth in SEQ ID NO. 7 and a light chain variable domain comprising CDRs as set forth in SEQ ID NO: 8;
d) a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 3, and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 4;
e) a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 5, and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 6; and
f) a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 7, and a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 8.
13. The method of claim 12 , wherein the recombinant fully human antibody comprises heavy chain/light chain variable domain sequences selected from the group consisting of SEQ ID NO. 3/SEQ ID NO. 4, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.
14. The method of claim 12 , wherein the fully human antibody Fab fragment comprises heavy chain/light chain variable domain sequences selected from the group consisting of SEQ ID NO. 3/SEQ ID NO. 4, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.
15. The method of claim 12 , wherein the fully human single chain human antibody comprises heavy chain/light chain variable domain sequences selected from the group consisting of SEQ ID NO. 3/SEQ ID NO. 4, SEQ ID NO. 5/SEQ ID NO. 6, and SEQ ID NO. 7/SEQ ID NO. 8.
16. The method of claim 12 , wherein the subject further has a disease is selected from the group consisting of a burn wound infection, a surgical site infection, a diabetic foot ulcer, an infected wound, and cystic fibrosis.
17. A method for treating a subject having a Pseudomonas aeruginosa infection comprising administering an effective amount of the recombinant, fully human antibody of claim 1 to the subject.
18. The method of claim 17 , wherein the subject further has a disease selected from the group consisting of a burn wound infection, a surgical site infection, a diabetic foot ulcer, an infected wound, and cystic fibrosis.
19. A method for treating a subject having a Pseudomonas aeruginosa infection, said method comprising administering an effective amount of the recombinant fully human anti-OprF antibody, or antigen binding fragment thereof, of claim 4 to the subject.
20. The method of claim 19 , wherein the subject further has a disease selected from the group consisting of a burn wound infection, a surgical site infection, a diabetic foot ulcer, an infected wound, and cystic fibrosis.
21. The recombinant fully human anti-OprF antibody of claim 3 , wherein the antibody is an IgG1 or an IgG4.
22. The recombinant fully anti-OprF human antibody, or an antigen-binding fragment thereof, of claim 4 , wherein the antibody, or antigen-binding fragment, is classified as an isotype selected from the group consisting of: IgG, IgM, IgD, IgA, and IgE.
23. The recombinant fully anti-OprF human antibody, or an antigen-binding fragment thereof, of claim 22 , wherein the antibody, or antigen-binding fragment, is an IgG1 or an IgG4.
24. The recombinant fully human anti-OprF antibody, or an antigen-binding fragment thereof, of claim 4 , wherein the antibody, or antigen-binding fragment thereof, comprises a heavy chain variable domain and a light chain variable domain selected from the group consisting of
a) a heavy chain variable domain comprising the CDRs as set forth in SEQ ID NO. 3 and comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 3, and a light chain variable domain comprising the CDRs as set forth in SEQ ID NO. 4 and an amino acid sequence that is at least 95% identical to SEQ ID NO. 4;
b) a heavy chain variable domain comprising the CDRs as set forth in SEQ ID NO. 5, and an amino acid sequence that is at least 95% identical to SEQ ID NO: 5, and a light chain variable domain comprising the CDRs as set forth in SEQ ID NO. 6 and an amino acid sequence that is at least 95% identical to SEQ ID NO. 6; and
c) a heavy chain variable domain comprising the CDRs as set forth in SEQ ID NO. 7 and an amino acid sequence that is at least 95% identical to SEQ ID NO. 7, and a light chain variable domain comprising the CDRs as set forth in SEQ ID NO. 8 and an amino acid sequence that is at least 95% identical to SEQ ID NO. 8.
25. The recombinant anti-OprF human antibody, or antigen-binding fragment of claim 4 , wherein antibody, or antigen-binding fragment is a monoclonal antibody, a human antibody, a humanized antibody, an Fab, an Fab′, an F(ab′)2, an Fv, a domain antibody (dAb), a single-chain antibody (scFv), a chimeric antibody, a diabody, a triabody or a tetrabody.Cited by (0)
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